Open AccessPPAR γ silencing enhances osteogenic differentiation of human adipose‐derived mesenchymal stem cells
Author(s) -
Lee MonJuan,
Chen HuiTing,
Ho MeiLing,
Chen ChungHwan,
Chuang ShuChun,
Huang SungCheng,
Fu YinChih,
Wang GwoJaw,
Kang Lin,
Chang JeKen
Publication year - 2013
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12098
Subject(s) - mesenchymal stem cell , microbiology and biotechnology , gene silencing , adipose tissue , stem cell , adipogenesis , chemistry , biology , biochemistry , gene
Abstract Peroxisome proliferator‐activated receptor gamma (PPARγ) is the master regulator of adipogenesis, and has been indicated as a potential therapeutic target to promote osteoblast differentiation. However, recent studies suggest that suppression of PPAR γ inhibits adipogenesis, but does not promote osteogenic differentiation in human bone marrow‐derived mesenchymal stem cells ( hBMSC s). It was reasoned that the osteogenic effect of PPAR γ suppression may be masked by the strong osteogenesis‐inducing condition commonly used, resulting in a high degree of matrix mineralization in both control and experimental groups. This study investigates the role of PPAR γ in the lineage commitment of human adipose‐derived mesenchymal stem cells ( hADSC s) by interfering with the function of PPAR γ mRNA through small interfering RNA s (si RNA s) specific for PPAR γ2. By applying an osteogenic induction condition less potent than that used conventionally, we found that PPAR γ silencing led to retardation of adipogenesis and stimulated a higher level of matrix mineralization. The mRNA level of PPAR γ decreased to 47% of control 2 days after treatment with 50 nmol/l PPAR γ2 si RNA , while its protein expression was 60% of mock control. In the meantime, osteogenic marker genes, including bone morphogenic protein 2 ( BMP 2), runt‐related transcription factor 2 (Runx2), alkaline phosphatase ( ALP ) and osteocalcin ( OC ), were up‐regulated under PPAR γ silencing. Our results suggest that transient suppression of PPAR γ promotes the onset of osteogenesis, and may be considered a new strategy to stimulate bone formation in bone tissue engineering using hADSC s.